Antithrombotic therapy with fondaparinux in relation to interventional management strategy in patients with ST- and non-ST-segment elevation acute coronary syndromes: an individual patient-level combined analysis of the Fifth and Sixth Organization to Assess Strategies in Ischemic Syndromes (OASIS 5 and 6) randomized trials.
BACKGROUND
The Fifth and Sixth Organization to Assess Strategies in Ischemic Syndromes (OASIS 5 and 6) trials evaluated fondaparinux, a synthetic factor Xa inhibitor, in patients with non-ST- and ST-segment elevation acute coronary syndromes, respectively. Combined results for these 2 trials on major efficacy and safety outcomes and data on the effects of fondaparinux in relation to interventional management strategy have not been previously reported.


RESULTS
We performed an individual patient-level combined analysis of 26 512 patients from the OASIS 5 and 6 trials who were randomized in a double-blind fashion to fondaparinux 2.5 mg daily or a heparin-based strategy (dose-adjusted unfractionated heparin or enoxaparin). Results were stratified according to whether an early invasive, a delayed invasive, or an initial conservative management strategy was performed. Fondaparinux was superior to heparin in reducing the composite of death, myocardial infarction, or stroke (8.0% versus 7.2%; hazard ratio [HR], 0.91; P=0.03) and death alone (4.3% versus 3.8%; HR, 0.89; P=0.05). Fondaparinux reduced major bleeding by 41% (3.4% versus 2.1%; HR, 0.59; P<0.00001) and had a more favorable net clinical outcome than heparin (11.1% versus 9.3%; HR, 0.83; P<0.0001). In 19 085 patients treated with an invasive strategy, fondaparinux suppressed ischemic events to an extent similar to heparin and reduced major bleeding by more than one-half, resulting in a superior net clinical outcome (10.8% versus 9.4%; HR, 0.87; P=0.008). A similar benefit also was observed in those treated with a conservative strategy (HR, 0.74; 95% confidence interval, 0.64 to 0.85; P<0.001).


CONCLUSIONS
Compared with a heparin-based strategy, fondaparinux reduced mortality, ischemic events, and major bleeding across the full spectrum of acute coronary syndromes and was associated with a more favorable net clinical outcome in patients undergoing either an invasive or a conservative management strategy.
Mehta
Shamir R
SR
McMaster University, Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada. smehta@mcmaster.ca
Boden
William E
WE
Eikelboom
John W
JW
Flather
Marcus
M
Steg
P Gabriel
PG
Avezum
Alvaro
A
Afzal
Rizwan
R
Piegas
Leopoldo S
LS
Faxon
David P
DP
Widimsky
Petr
P
Budaj
Andrzej
A
Chrolavicius
Susan
S
Rupprecht
Hans-Jurgen
HJ
Jolly
Sanjit
S
Granger
Christopher B
CB
Fox
Keith A A
KA
Bassand
Jean-Pierre
JP
Yusuf
Salim
S
D054058:Acute Coronary Syndrome / Q000150:complications / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy*; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004562:Electrocardiography; D017984:Enoxaparin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D000077425:Fondaparinux; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D011134:Polysaccharides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D020521:Stroke / Q000209:etiology / Q000517:prevention & control; D016896:Treatment Outcome
D000925:Anticoagulants; D017984:Enoxaparin; D011134:Polysaccharides; D006493:Heparin; D000077425:Fondaparinux